Water → HCID 10072114, compound

HRID 73193Notes

Reaction equation

HRID 73193 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C:17]([CH:19]1[CH2:24][CH2:23][CH:22]([CH3:25])[CH2:21][CH:20]1[OH:26])=[O:18])[CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:4].O.[Li+].[OH-]>O1CCOCC1>[OH:26][CH:20]1[CH2:21][CH:22]([CH3:25])[CH2:23][CH2:24][CH:19]1[C:17]([N:10]([CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[C:9]1[CH:8]=[C:7]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2])=[O:18]

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 68423065HCID 68423065, compound

Product 1

HCID 10072114HCID 10072114, compoundYield 52%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-[(2-Hydroxy-4-methyl-cyclohexanecarbonyl)-(tetrahydro-pyran-4-yl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester (31 mg, 0.062 mmol) was dissolved in a 4:1 mixture of dioxane:H2O (0.6 ml) and then LiOH 1N (310 ul, 0.310 mmol) was added. After 4 hours of stirring at room temperature, solvents were removed and then partitioned between 5 ml of H2O acidified to pH 4 and 5 ml of EtOAc. The organic layer was separated and the aqueous phase was washed twice with ethyl acetate (2×5 mL). The combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC to obtain 14 mg (52%) of 3-[(2-Hydroxy-4-methyl-cyclohexanecarbonyl)-(tetrahydro-pyran-4-yl)-amino]-5-phenyl-thiophene-2-carboxylic acid (Compound 31).

Workup

  1. customsolvents were removed
  2. custompartitioned between 5 ml of H2O
  3. customThe organic layer was separated
  4. washthe aqueous phase was washed twice with ethyl acetate (2×5 mL)
  5. dry with materialThe combined ethyl acetate layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c0c25dbfb0754c91947fcfb91946622b
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

Loading…